Inducible transcription factors (ITFs) within vestibular neurons are expressed under a variety of conditions associated with vestibular adaptation. Based on preliminary findings, a set of experiments is proposed to examine the functional relationship between ITF expression and adaptation of the vestibulo-ocular response (VOR) to horizontal head rotation or translation in gerbils. We will adapt the VOR gain in alert gerbils using two conditions of visual/vestibular mismatch: 1) fixed, or, 2) reversed visual surround during sinusoidal whole body motion (rotational or translational) to induce VOR gain reduction or enhancement, respectively. Vestibulo-ocular and vestibulospinal neurons will be retrogradely labeled from the abducens nuclei and cervical cord. Subsequently, the brain will be fixed and prepared for ITF (e.g. Fos) immunohistochemistry and tracer location. Using data from these baseline experiments, additional studies using the same approach will determine whether blockade of Fos expression by regional microinjection with antisense oligonucleotides results in a modification of VOR adaptation and concurrent blockade of Fos expression. We hypothesize that ITFs such as Fos will be expressed in specific vestibular nuclei and cerebellar cortical neurons in response to gain adaptation of the VOR. The blockade of ITF expression in VOR neurons will prevent VOR adaptation but will not alter baseline VOR responses. Furthermore, we hypothesize that only particular functional types will double label for the Fos ITF and retrograde tracer. The data should provide a functional correlate between a molecular marker and the modified VOR that defines vestibular adaptation. Finally, we will address the issue of adaptation retention by measuring the VOR over several days following a single adaptation stimulus, determining the time for the VOR gain to asymptote to normal, and then repeating the adaptation stimulus, followed by ITF analysis. We hypothesize that the ITF expression after such training will be reduced, or in different locations from that of na[unreadable]ve animals. These findings could provide evidence regarding how the brain develops sensorimotor sets appropriate for two environments.